Background: The presence and severity of patent ductus arteriosus (PDA) are difficult to assess continuously in preterm neonates. PDA is associated with altered blood pressure (BP) and heart rate (HR). These two variables affect the time between the ECG R wave and the corresponding following systolic peak of the BP waveform (T). Cardiac cycle length (L) is readily measured from the ECG. The ratio T:L gives a dimensionless index that is HR independent and is expressed by the phase difference. Hypothesis: PDA size is related to phase difference.

Methods: Extremely preterm infants <29 weeks’ gestation without pre-existing severe intraventicular haemorrhage or other congenital malformations. ECG, invasive aortic BP monitoring and echocardiography were measured in the first three days after birth using IntelliVue MX800 monitors (Philips Healthcare, UK). The ECG and BP traces were downloaded to a PC using IxTrend software (Ixellence GmbH, Germany). PDA size was measured by echocardiography. Software was written using MATLAB (The MathWorks Inc., USA) to import and analyse the data. The difference in time between the ECG R wave and the following systolic blood pressure peak was measured and expressed as phase, i.e. the proportion of one cardiac cycle. The study was funded by Neocirculation consortium (European FP7-Grant N:282533). The study protocol was approved by North West- Lancaster ethics committee, REC reference: 14/NW/1274.

Results: 15 infants were studied either on Day 2 or Day 3 after birth and a single measurement was analysed for each infant. Median (Interquartile range) birth weight 0.89 kg (0.76-1.15), gestation 26.3 weeks (24.9-28.1), PDA size 1.6 mm (1.2-2.5), BP 36 mmHg (30-41). The analysis included four neonates who received inotropes, one who subsequently had a severe intraventricular haemorrhage and three who later died. There was a significant positive correlation between phase difference and PDA size (Spearman’s rho=0.714, P=0.003). Phase difference did not correlate with birth weight, gestation or BP.

Conclusion: A significant relation between the phase difference and PDA size in extremely preterm neonates was observed. The time difference between ECG and BP is straightforward to measure and hence the results of this pilot study suggest that this approach merits further investigation as a possible biomarker in trend monitoring of PDA size and function.

We acknowledge Dave Cordon (medical engineer in Liverpool Women’s Hospital), Tristan Payne and Matt Elt (electrical engineers in Royal Liverpool Hospital) for installing and supporting the IT systems for data downloading and extraction.